Saturated and unsaturated 17-formyl-cyclopentanopolyhydrophenanthrenes



UNITED STATES PATENT OFFICE SATURATED AND UNSATURATED 17- FORMYL CYCLOPENTANOPOLYHYDRO- PHENANTHRENES- Tadeus Reichstein, Zurich, Switzerland, assignor, by mesne assignments, to Ciba Pharmaceutical Products, Incorporated, Summit, N. J., a corporation of New Jersey No Drawing. Application July 25, 1938, Serial No. 221,238. In Switzerland July 25, 1937 6 Claims. (01. 260-3914) By this invention saturated and unsaturated purposes or as intermediate products in the proderivatives of 1'7-formyl-cyclopentanopolyhydroduction of such substances.

ph na hr n s a o i y vertin in The following example illustrates the invensaturated or unsaturated derivatives of 17-ca1' tion, the parts being by Weight:

boxycyclopentanopolyhydrophenanthrenes the 5 Example carboxyl group into the aldehyde group with aid of reducing agents. 1 part of 13 -3-acetoxy-etio-cholenic acid The expression cyclopentanopolyhydrophen- (melting point 242 C. corrected) is dissolved in anthrene compounds includes for example comparts of benzene and the solution is cautiously pounds of the type of etio-cholane, estrane, hy- 10 boiled with 4 parts of thionyl chloride. After dro-estrane, or their stereoisomers. The eticabout 2 hours evolution o hydrDgeh chloride and acids used as parent materials may contain fur- Sulfur d o de has c sed- Should a y p r n y ther substituents in the ring system, for example S e y s av S p t ey are removed;

f ee or substituted hydroxyl-, carbinoland they constitute the anhydride of the acetylated amino-groups, further keto-groups and their 15 a id and m y be r o v t d t h par nt enol derivatives, such as enol ester and enol p du t y sa n fi at n and ty t Th ether, halogen atoms or also hydrocarbon radibenzene solution is evaporated under reduced cals. In addition to the carboxyl-group the 1'?- pressure and the residue is dissolved in parts carbon atom may contain'for example hydroof P y y After addition of 1 p Of gen and particularly a free or substituted hydrox- Z0 P a a Sulfate (Containing ut 2 yl group. per cent of palladium) dry purified hydrogen is The reduction according to the present process introduced into the solution at boiling temperama be carried out in known manner. Referture in a re ux apparat s and t fi u nt as is ence is made in this connection for example passed hr h wa containing some m y to the text-book Die Methoden der organishen orange. To this caustic soda solution is added Chemie of Houben-Weyl, 3rd edition, volume II, gradually d s the qu n y of hydro en pages 287-293. chloride split ofi is determined. As soon as 50 The procedure may consist in converting the p cent of the Calculated q n ty has been split carboxyl group into the acid chloride, if required ofi the p c s is nte pte he react on m after protecting oXy groups present in the ring ture is filtered, the filtrate is concentrated under system by acylation or etherification, and then reduced pressure to a small volume, a mixture of subjecting the acid chloride to catalytic reducequal parts of dioxane and sulfuric acid of 20 tion. Or the acid may be converted into an acid per cent strength is added and the whole is anilide or substituted acid anilide, this may be heated to boiling for 1 hour in a reflux apparatus. converted by the action of phosphorus penta- Then the dioxane is removed as far as possible halide into an imidohalide and the latter reduced, under red ed pr ss w h ted addition of for example with stannous chloride and hydrowater, the reaction product is extracted with chloric acid. Advantageously the product is then ether and from the ethereal solution the acid subjected to acid hydrolysis. Other known mwhich has not entered into reaction is recovered ducing agents, such as chromous salts are also (as the free oxy acid melting at 280 C'., corrected,

suitable, with decomposition) by extraction with sodium The reaction may be illustrated by way of excarbonate solution; it may be used for a fresh reample by the following scheme: action. From the neutral product the A -3-hy- CH3 CH3 CH3 CH3 CH3 CH3 cool CH0 CH0 @IT t l A o I I A o I I no I The products are useful for the preparation of droxy-17-formyl-etio-cholene can be recovered substances which are valuable for therapeutical in the usual manner either directly or after puri- 2. A process for the manufacture of saturated I and unsaturated 17-formyl-cyclopentanopolyhydrophenanthrenes, which comprises converting the carboxylic acid group of derivatives of saturated and unsaturated 17-carboxy-cyc1opentanopolyhydrophenanthrenes into an acid halide In analogous manner there are' group and then converting the latter into an aldehyde group with aid of a reducing agent capable of effecting such conversion.

3. The compounds of the following formula:

CH3 CH3 4. A -3-hydroxy-l'l-formyl-etio-cholene.

5. A -3-acetoxy-17-formy1-etio cholene.

6. A compound of the group consisting of the saturated and unsaturated 17-f0rmy1-1'1-H-cyclopentano 10,13-dimethy1 polyhydrophenanthrenes.

TADEUS REICHSTEIN. 

